Varicella zoster virus (VZV) is, by virological standards, one of the most successful human herpesviruses. It infects the great majority of the population in childhood and remains latent in ganglia to reappear as zoster in aging populations. It also causes serious ocular disease that can result in blindness. While VZV spreads efficiently in the host, it is still, despite much effort on the part of virologists, difficult to handle in the laboratory. Little is known of the proteins that regulate the VZV infectious cycle. In this proposal we plan to address several aspects of VZV gene expression (particularly the expression of the first genes made in the infected cell) and regulation in the context of both viral development in the infected cell and of the host's immune response to infection. There are four specific aims. In the first of these, we plan to continue preliminary studies to define regulatory proteins of VZV that are incorporated into the virion structure. In the second aim, we will explore the regulation of the first genes expressed in infection and define the possible function of structural proteins on their expression. In the third aim, we will investigate the functions of IE62 in more detail with intention of defining the parts of the protein responsible for its function, thereby generating a picture of the functional make-up of this large protein. In the fourth aim, we will define the importance of IE62 in the generation of the VZV-specific immune response, particularly as it relates to protection of the host from VZV infection.